Darunavir is a potent HIV protease inhibitor belonging to the class of hydroxyethyl amino sulfonamides. Darunavir is known by chemical name [(1S,2R)-3-[[(4-aminophenyl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester. Darunavir is generically disclosed in U.S. Pat. No. 5,843,946 and specifically disclosed in U.S. Pat. No. 6,248,775.
The ethanol solvate of darunavir, referred as Darunavir ethanolate is represented by following structure:

Darunavir ethanolate is marketed in USA by Tibotec Pharmaceuticals under the trade name Prezista® and is specifically covered by U.S. Pat. No. 7,700,645.
We observed that very few references are directed towards synthesis of darunavir. The product patent U.S. Pat. No. 6,248,775 B2 does not provide any enabling disclosure for preparation of darunavir (1).
The process described in the publication Dominique et. al; Journal of Medicinal Chemistry, 2005, 48(6), 1813-1822 and the patent application US 2007/060642 A1 which involves condensation of diamino compound (2) with furanyl derivative (3) is most relevant to the present invention and is depicted in scheme 1 below.

The synthesis of darunavir (1) by coupling of diamino compound (2) with furanyl derivative (3) very likely leads to formation of impurities, viz., impurity A and impurity B. However, the formation of these impurities A and B is not mentioned in any of the prior art references. The structural formulae of impurity A and impurity B are as represented below:

These impurities can form due to presence of 4-amino group in the 4-aminophenylsulfonyl group on the tertiary nitrogen of diamino compound (2), since it can react with furanyl derivative (3). Due to prevalence of these impurities the process of above mentioned prior art is less desired and there is a need to develop an improved process.
The publication Dominique et. al; Journal of Medicinal Chemistry, 2005, 48(6), 1813-1822 further discloses preparation of nitro compound (5) by reaction of amino compound (4) with furanyl derivative (3) (where R=succinimidyl group) in presence of triethylamine in tetrahydrofuran to obtain nitro compound (5). Surprisingly, this publication does not provide any suggestions for reduction of nitro compound (5) to obtain darunavir (1). The process disclosed in this publication is depicted in the synthetic scheme 2.

The inventors of the present invention have developed a novel process, which not only avoids formation of impurities A and B but also performs reduction of nitro compound (5) under selective condition in such a way that decomposition of carbamate linkage occurs to a lesser extent.
It is well known that particle size can affect the solubility properties of a pharmaceutical compound. Particle size reduction can increase a compound's dissolution rate and consequently its bioavailability. Particle size can affect how freely the crystals or powdered form of the drug will flow past each other, which has consequence in production process of pharmaceutical products containing the drug. The inventors of the present invention have developed darunavir ethanolate of fine particle size, which has good solubility and is well suited for preparing pharmaceutical products.